C-centered Radicals Research Articles

Nickel/Iridium Metallaphotoredox Catalysis for Allylic C-H Bond Arylation of N-Allyl Heterocycles.

Despite conceptual breakthroughs in dual photoredox- and nickel-catalyzed arylation of radicals, the approach remains largely limited to localized C-centered radicals. Here, we extend it to allylic radicals, focusing on N-allyl heterocycles. Using [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 and NiCl2(dtbbpy) under visible light, we achieve regioselective γ-amino radical arylation, yielding enamines in good yields. In some cases, in situ photoisomerization produces the Z isomer, influenced by the substrate and the triplet state energy of the photocatalyst.

Radical Polarity.

The polarity of a radical intermediate profoundly impacts its reactivity and selectivity. To quantify this influence and predict its effects, the electrophilicity/nucleophilicity of >500 radicals has been calculated. This database of open-shell species entails frequently encountered synthetic intermediates, including radicals centered at sp3, sp2, and sp hybridized carbon atoms or various heteroatoms (O, N, S, P, B, Si, X). Importantly, these computationally determined polarities have been experimentally validated for electronically diverse sets of >50 C-centered radicals, as well as N- and O- centered radicals. High correlations are measured between calculated polarity and quantified reactivity, as well as within parallel sets of competition experiments (across different radical types and reaction classes). These multipronged analyses show a strong relationship between the computed electrophilicity, ω, of a radical and its relative reactivity (krel vs Δω slopes up to 40; showing mere Δω of 0.1 eV affords up to 4-fold rate enhancement). We expect this experimentally validated database will enable reactivity and selectivity prediction (by harnessing polarity-matched rate enhancement) and assist with troubleshooting in synthetic reaction development.

Visible-Light-Mediated Trifluoroalkylation of Isoquinolines via Three-Component Minisci-Type Reaction.

A sustainable photocatalytic approach has been established for trifluoroalkylation of isoquinoline via a three-component Minisci-type reaction using a green solvent. The polarity reversal radical cascade strategy renders the selective addition of an electrophilic CF3 radical to an olefin to forge a nucleophilic C-centered radical. This multicomponent approach is operationally simple and environmentally benign with various functional groups, viz. aldehydes, acetals, amides, and halides. Mechanistic investigations were carried out to elaborate the reductive quenching catalytic pathway.

Remote Functionalization of Inert C(sp3)-H Bonds via Dual Catalysis Driven by Alkene Hydrofluoroalkylation Using Industrial Feedstocks.

We have developed a dual-catalytic system capable of site-selective azidation of inert C(sp3)-H bonds with concomitant and modular anti-Markovnikov alkene fluoroalkylation. The protocol leverages the synergetic cooperation of both the photocatalyst and earth-abundant iron catalyst to deliver two radical species in succession to minimally functionalized alkenes. This powerful catalyst system exhibits broad scope, mild conditions, and excellent regioselectivity for a variety of substrates and fluoroalkyl fragments. The key to this C-centered radical relay is the matched rate of both photocatalytic and iron catalytic cycles, ensuring selective azidofluoroalkylation with a broad array of fluoroalkyl sources from trivial reagents.

Structure and Kinetics of Organic Acid Radicals Formed in Reaction with •OH Radicals.

The study investigated •OH-derived radicals from certain organic acids employed in nuclear fuel processing and separation using EPR spectroscopy and quantum chemistry methods. Hydroxyl radicals were generated through a Fenton-like reaction within the EPR resonator under both acidic and basic conditions, allowing for the detection of neutral and radical anions, respectively. The spectral assignment and analysis were conducted using a combination of literature data and quantum chemical calculations employing DFT theory with B3LYP or LPBE functionals and the L2a_3 basis set. The reaction of the •OH radical with lactic and glycolic acids yielded primary C-centered radicals through hydrogen abstraction from these acids. In contrast, the •OH radical exclusively generated secondary radicals from oxalic acid, whereas for citric acid, it resulted in both primary and secondary species induced by decarboxylation. The EPR spectrum of acetohydroxamic acid, upon reaction with the •OH radical, displayed a complex pattern featuring primary •N-type and N-O•-type radicals. The decay pathways of the generated radicals were primarily attributed to radical-radical reactions, with the extracted reaction rate constants generally falling within the typical range observed for such reactions. The EPR parameters calculated for potential radicals using B3LYP and LPBE functionals with L2a_3 basis set demonstrated good accuracy for neutral radicals, albeit requiring minor adjustments for radical anions.

Solubility Change Behavior of Fluoroalkyl Ether-Tagged Dendritic Hexaphenol under Extreme UV Exposure.

This study focuses on the discovery of a single-component molecular resist for extreme ultraviolet (EUV) lithography by employing the ionizing radiation-induced decomposition of carbon-fluorine chemical bonds. The target material, DHP-L6, was synthesized by bonding perfluoroalkyl ether moieties to amorphous dendritic hexaphenol (DHP) with a high glass transition temperature. Upon exposure to EUV and electron beam irradiation, DHP-L6 films exhibited a decreasing solubility in fluorous developer media, resulting in negative-tone images. The underlying chemical mechanisms were elucidated by Fourier transform-infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy, and nanoindentation experiments. These analyses highlighted the possible electron-induced decomposition of C-F bonds in DHP-L6, leading to molecular network formation via recombination of the resulting C-centered radicals. Subsequent high-resolution lithographic patterning under EUV irradiation showed that DHP-L6 could create stencil patterns with a line width of 26 nm at an exposure dose of 110 mJ cm-2. These results confirm that single-component small molecular compounds with fluoroalkyl moieties can be employed as patterning materials under ionizing radiation. Nonetheless, additional research is required to reduce the relatively high exposure energy for high-resolution patterning and to enhance the line-edge roughness of the produced stencil.

Visible light-driven molecular oxygen activation by lead-zinc smelting slag and tartaric acid for efficient organic pollutant degradation and Cr(VI) reduction

The remediation of heavy metal and organic-contaminated wastewater remains a significant concern in environmental science, necessitating the development of cost-effective and efficient treatment systems. This study focuses on the setup of a highly effective molecular oxygen (O2) activation system using lead–zinc smelting slag (LZSS) and tartaric acid (TA) under visible light. The LZSS-TA complex exhibited rapid photochemical reactions and demonstrated a remarkable capacity for O2 activation, resulting in the in situ generation of hydrogen peroxide (H2O2) and 99 % degradation of para-chloroaniline (p-CA). The formation of H2O2 occurred through a two-step single electron transfer pathway, whereby C-centered radicals (CHOHCHOHCOO−) generated within the system initiated the reduction of O2 to form O2−, as a crucial intermediate. The produced O2− is then reduced by Fe(II) to generate H2O2 via proton-coupled electron transfer (PCET) processes. Light-induced ligand-to-metal charge transfer (LMCT) process is the key to the production of C-centered radicals and Fe(II), which determines the production efficiency of H2O2 and OH. Additionally, this system enabled simultaneous oxidation of p-CA by 98 % and reduction of Cr(VI) by 100 % within 60 min. More importantly, O2 activation by TA-assisted LZSS under natural sunlight/solar irradiation could efficiently degrade p-CA in both ultrapure water (94 %) and reservoir water (92.5 %) within 210 min. This study significantly contributes to the understanding of light-driven O2 activation and lays the foundation for the design of cost-effective and efficient pollution remediation systems.

Sulfonamides as N-Centered Radical Precursors for C-N Coupling Reactions To Generate Amidines.

Nitrogen-centered radicals (NCRs) are valuable intermediates for the construction of C-N bonds. Traditional methods for the generation of NCRs employ toxic radical initiators, transition metal catalysts, photocatalysts, or organometallic reagents. Herein, we report a novel strategy for the generation of NCRs toward the construction of C-N bonds under transition-metal-free conditions. Thus, super-electron-donor (SED) 2-azaallyl anions undergo single-electron transfer (SET) with sulfonamides, forming aminyl radicals (R2N•, R = alkyl) and culminating in the generation of amidines bearing various functional groups (33 examples, up to 96% yield). Broad substrate scope and gram-scale telescoped preparation demonstrate the practicality of this method. Radical clock and electron paramagnetic resonance (EPR) experiments support the proposed radical coupling pathway between the generated N-centered radical and the C-centered 2-azaallyl radical.

Producing Conventional and Transient Amino(mercapto)methyl Radicals by Addition of Muonium to a Crystalline Thioformamide (Mes*NHCH=S).

Muonium (Mu=μ+e-) is composed of a muon of light isotope of proton (μ+) and electron (e-) and can be used as a light surrogate for a hydrogen atom. In this paper, we investigated addition of muonium to a newly synthesized Mes*-substituted thioformamide (Mes*NHCH=S, Mes*=2,4,6-tBu3C6H2). Transverse-field muon spin rotation (TF-μSR) of a solution sample of the thioformamide confirmed addition of muonium to the sulfur atom leading to the corresponding C-centered radical [Mes*NHC(H)⋅-SMu]. Density functional theory (DFT) calculations assigned a conventional amino(mercapto)methyl radical, in which both nitrogen and carbon were slightly pyramidalized, and the calculated muon hyperfine coupling constant (hfcc) including the muon isotope effect was compatible with the experimentally determined parameter. However, the muon level-crossing resonance (μLCR) spectrum of an anisotropic crystalline sample indicated two paramagnetic species, and the major product showed the considerably larger muon hfcc compared with the conventional structure of the amino(mercapto)methyl radical. The unusual transient muoniated thioformamide with the larger muon hfcc that showed rapid relaxation could be only explained by a transient structure including planarization of the nitrogen and carbon atoms in Mes*NHC(H)⋅-SMu.

Regioselective Rearrangement of Nitrogen- and Carbon-Centered Radical Intermediates in the Hofmann-Löffler-Freytag Reaction.

The Hofmann-Löffler-Freytag (HLF) reaction serves as a late-stage functionalization technique for generating pyrrolidine heterocyclic ring systems. Contemporary HLF protocols utilize in situ halogenated sulfonamides as precursors in the radical-mediated rearrangement cycle. Despite its well-established reaction mechanism, experiments toward the detection of radical intermediates using EPR techniques have only recently been attempted. However, the obtained spectra lack the distinct features of the N-centered radicals expected for the employed reactants. This paper presents phenylbutylnitrone spin-trapped C-centered and N-centered radicals, generated via light irradiation from N-halogen-tosyl-sulfonamide derivatives and detected using EPR spectroscopy. NMR spectroscopy and DFT calculations are used to explain the observed regioselectivity of the HLF reaction.

Theoretical Insights into the Gas-Phase Oxidation of 3-Methyl-2-butene-1-thiol by the OH Radical: Thermochemical and Kinetic Analysis.

3-Methyl-2-butene-1-thiol ((CH3)2C═CH-CH2-SH; MBT) is a recently identified volatile organosulfur compound emitted from Cannabis sativa and is purported to contribute to its skunky odor. To understand its environmental fate, hydroxyl radical (•OH)-mediated oxidation of MBT was conducted using high-level quantum chemical and theoretical kinetic calculations. Three stable conformers were identified for the title molecule. Abstraction and addition pathways are possible for the MBT + OH radical reaction, and thus, potential energy surfaces involving H-abstraction and •OH addition were computed at the CCSD(T)/aug-cc-pV(T+d)Z//M06-2X/aug-cc-pV(T+d)Z level of theory. The barrier height for the addition of the OH radical to a C atom of the alkene moiety, leading to the formation of a C-centered MBT-OH radical, was computed to be -4.1 kcal mol-1 below the energy of the starting MBT + OH radical-separated reactants. This reaction was found to be dominant compared to other site-specific H-abstraction and addition paths. The kinetics of all the site-specific abstraction and addition reactions associated with the most stable MBT + OH radical reaction were assessed using the MESMER kinetic code between 200 and 320 K. Further, we considered the contributions from two other conformers of MBT to the overall reaction of MBT + OH radical. The estimated global rate coefficient for the oxidation of MBT with respect to its reactions with the OH radical was found to be 6.1 × 10-11 cm3 molecule-1 s-1 at 298 K and 1 atm pressure. The thermodynamic parameters and atmospheric implications of the MBT + OH reaction are discussed.

Radical dehydroxymethylative fluorination of aliphatic primary alcohols and diverse functionalization of α-fluoroimides via BF3·OEt2-catalyzed C‒F bond activation

Ag2CO3-promoted dehydroxymethylative fluorination of aliphatic alcohols has been achieved with Selectfluor as both oxidant and fluorine source. The reaction involves β-fragmentation of primary alkoxy radicals, followed by the fluorination of the resulting C-centered radical intermediates. The transformation proceeds under mild reaction conditions and exhibits a broad substrate scope, thus opening up a new entrance to the synthesis of fluorinated constructs including α-fluoroimides and 1-fluoroalkyl benzoates as well as secondary and tertiary alkyl fluorides like versatile 2-fluoro-2-alkyl 1,3-propandiol derivatives. The divergent functionalization of the obtained α-fluoroimides enables an efficient access to amine derivatives through C–F bond activation under the action of BF3·OEt2.

Electrochemical Formation of Oxazolines by 1,3-Oxyfluorination of Non-activated Cyclopropanes.

The C-C bond in non-activated cyclopropanes can be intramolecularly cleaved with an electrochemically generated amidyl radical forming oxazolines. In the presence of TBABF4, this provides 1,3-oxyfluorination products. C-C bond cleavage of cyclopropane proceeds with inversion of the configuration, suggesting an intramolecular homolytic substitution (SHi) mechanism. The performance of TBABF4 as an efficient fluoride source was explained by accumulation of the BF4- anion at the anode surface, at which a carbocation is formed by the oxidation of the C-centered radical.

Radical S-Adenosyl-l-Methionine Enzyme PylB: A C-Centered Radical to Convert l-Lysine into (3R)-3-Methyl-d-Ornithine.

PylB is a radical S-adenosyl-l-methionine (SAM) enzyme predicted to convert l-lysine into (3R)-3-methyl-d-ornithine, a precursor in the biosynthesis of the 22nd proteogenic amino acid pyrrolysine. This protein highly resembles that of the radical SAM tyrosine and tryptophan lyases, which activate their substrate by abstracting a H atom from the amino-nitrogen position. Here, combining in vitro assays, analytical methods, electron paramagnetic resonance spectroscopy, and theoretical methods, we demonstrated that instead, PylB activates its substrate by abstracting a H atom from the Cγ position of l-lysine to afford the radical-based β-scission. Strikingly, we also showed that PylB catalyzes the reverse reaction, converting (3R)-3-methyl-d-ornithine into l-lysine and using catalytic amounts of the 5'-deoxyadenosyl radical. Finally, we identified significant in vitro production of 5'-thioadenosine, an unexpected shunt product that we propose to result from the quenching of the 5'-deoxyadenosyl radical species by the nearby [Fe4S4] cluster.

Construction of C-S and C-Se Bonds from Unstrained Ketone Precursors under Photoredox Catalysis.

A mild photoredox catalyzed construction of sulfides, disulfides, selenides, sulfoxides and sulfones from unstrained ketone precursors is introduced. Combination of this deacylative process with SN 2 or coupling reactions provides novel and convenient modular strategies toward unsymmetrical or symmetric disulfides. Reactivity studies favor a bromine radical that initiates a HAT (Hydrogen Atom Transfer) from the aminal intermediate resulting in expulsion of a C-centered radical that is intercepted to make C-S and C-Se bonds. Gram scale reactions, broad substrate scope and tolerance towards various functional groups render this method appealing for future applications in the synthesis of organosulfur and selenium complexes.

Chiral arylsulfinylamides as reagents for visible light-mediated asymmetric alkene aminoarylations.

Two- or one-electron-mediated difunctionalizations of internal alkenes represent straightforward approaches to assemble molecular complexity by the simultaneous formation of two contiguous Csp3 stereocentres. Although racemic versions have been extensively explored, asymmetric variants, especially those involving open-shell C-centred radical species, are much more limited both in number and scope. Here we describe enantioenriched arylsulfinylamides as all-in-one reagents for the efficient asymmetric, intermolecular aminoarylation of alkenes. Under mild photoredox conditions, nitrogen addition of the arylsulfinylamide onto the double bond, followed by 1,4-translocation of the aromatic ring, produce, in a single operation, the corresponding aminoarylation adducts in enantiomerically enriched form. The sulfinyl group acts here as a traceless chiral auxiliary, as it is eliminated in situ under the mild reaction conditions. Optically pure β,β-diarylethylamines, aryl-α,β-ethylenediamines and α-aryl-β-aminoalcohols, prominent motifs in pharmaceuticals, bioactive natural products and ligands for transition metals, are thereby accessible with excellent levels of regio-, relative and absolute stereocontrol.

Unraveling how Fe-Mn modified biochar mitigates sulfamonomethoxine in soil water: The activated biodegradation and hydroxyl radicals formation

This study indicated that the application of a novel Fe-Mn modified rice straw biochar (Fe/Mn-RS) as soil amendment facilitated the removal of sulfamonomethoxine (SMM) in soil water microcosms, primarily via activating degradation mechanism rather than adsorption. The similar enhancement on SMM removal did not occur using rice straw biochar (RS). Comparison of Fe/Mn-RS with RS showed that Fe/Mn-RS gains new physic-chemical properties such as abundant oxygenated C-centered persistent free radicals (PFRs). In the Fe/Mn-RS microcosms, the degradation contributed 79.5–83.8% of the total SMM removal, which was 1.28–1.70 times higher than that in the RS microcosms. Incubation experiments using sterilized and non-sterilized microcosms further revealed that Fe/Mn-RS triggered both the biodegradation and abiotic degradation of SMM. For abiotic degradation of SMM, the abundant •OH generation, induced by Fe/Mn-RS, was demonstrated to be the major contributor, according to EPR spectroscopy and free radical quenching experiments. Fenton-like bio-reaction occurred in this process where Fe (Ⅲ), Mn (Ⅲ) and Mn (Ⅳ) gained electrons, resulting in oxidative hydroxylation of SMM. This work provides new insights into the impacts of biochar on the fates of antibiotics in soil water and a potential solution for preventing antibiotic residues in agricultural soil becoming a non-point source pollutant.

Unveiling the chemical kinetics of aminomethanol (NH2CH2OH): insights into H and O2 photo-oxidation reactions and formamide dominance.

Aminomethanol is released into the atmosphere through various sources, including biomass burning. In this study, we have expounded the chemical kinetics of aminomethanol in the reaction pathways initiated by the hydroxyl radical ( H) with the aid of ab initio//density functional theory (DFT) i.e., coupled-cluster theory (CCSD(T))//hybrid-DFT (M06-2X/6-311++G (3df, 3pd). We have explored various possible directions of the H radical on aminomethanol, as well as the formation of distinct pre-reactive complexes. Our computational findings reveal that the H transfer necessitates activation energies ranging from 4.1 to 6.5kcal/mol from the -CH2 group, 3.5-6.5kcal/mol from the -NH2 group and 7-9.3kcal/mol from the -OH group of three rotational conformers. The H transfer from -CH2, -NH2 and -OH exhibits an estimated total rate constant (k OH) of approximately 1.97 × 10-11cm3 molecule-1s-1 at 300K. The branching fraction analysis indicates a pronounced dominance of C-centered NH2 HOH radicals with a favorability of 77%, surpassing the N-centered HCH2OH (20%) and O-centered NH2CH2 (3%) radicals. Moreover, our investigation delves into the oxidation of the prominently favored carbon-centered NH2 HOH radical through its interaction with atmospheric oxygen molecules. Intriguingly, our findings reveal that formamide (NH2CHO) emerges as the predominant product in the NH2 HOH + 3O2 reaction, eclipsing alternative outcomes such as amino formic acid (NH2COOH) and formimidic acid (HN = C(H)-OH). At atmospheric conditions pertinent to the troposphere, the branching fraction value for the formation of formamide is about 99%, coupled with a rate constant of 5.5 × 10-12cm3 molecule-1 s-1. Finally, we have scrutinized the detrimental impact of formamide on the atmosphere. Interaction of formamide with atmospheric hydroxyl radicals could give rise to the production of potentially perilous compounds such as HNCO. Further, unreacted HCH2OH radicals may initiate the formation of carcinogenic nitrosamines when reacting with trace N-oxides (namely, NO and NO2). This, in turn, escalates the environmental risk factors.

Iodine-catalyzed intermolecular 1,2-thio (seleno)amination of alkenes with 1,2,3-triazoles and disulfides (diselenides) in air

Iodine-catalyzed 1,2-thio (seleno)amination of alkenes via direct N- and C-centered radical cross-coupling was established to elicit highly regioselective β-triazolized thioalkyl compounds.

Hydroalkylation of styrenes enabled by boryl radical mediated halogen atom transfer.

In this study, we present an inexpensive, stable, and easily available boryl radical source (BPh4Na) employed in a Halogen Atom Transfer (XAT) methodology. This mild and convenient strategy unlocks the use of not only alkyl iodides as radical precursors but also of the more challenging alkyl and aryl bromides to generate C-centered radicals. The generated radicals were further engaged in the anti-Markovnikov hydroalkylation of electronically diverse styrenes, therefore achieving the formation of C(sp3)-C(sp3) and C(sp3)-C(sp2) bonds. A series of experimental and computational studies revealed the prominent role of BPh4Na in the halogen abstraction step.